Field of the Invention
The present application relates generally to substrates that facilitate the administration of stem cells to target tissues in the context of stem cell therapy as well as to tools for manipulating and implanting such substrates into a target tissue.
Description of the Related Art
The scope of human disease that involves loss of or damage to cells is vast and includes, but is not limited to, ocular disease, neurodegenerative disease, endocrine diseases, cancers, and cardiovascular disease. Cellular therapy involves the use of cells, and in some cases stem cells to treat diseased or damaged tissues. It is rapidly coming to the forefront of technologies that are poised to treat many diseases, in particular those that affect individuals who are non-responsive to traditional pharmacologic therapies.
In fact, many diseases that are candidates for application of cellular therapy are not fatal, but involve loss of normal physiological function. For example, ocular diseases often involve functional degeneration of various ocular tissues which affects the vision, and thus the quality of life of numerous individuals.
The mammalian eye is a specialized sensory organ capable of converting incoming photons focused by anterior optics (cornea and lens) into a neurochemical signal. This process of phototransduction allows for sight by sending action potentials to higher cortical centers via the optic nerve. The retina of the eye comprises photoreceptors that are sensitive to various levels of light and interneurons that relay signals from the photoreceptors to the retinal ganglion cells. These photoreceptors are the most metabolically active cells in the eye (if not the body), and are supported metabolically and functionally by retinal pigmented epithelial cells (RPE). These RPE are positioned in a monolayer in the eye and are critical to vision.
Numerous pathologies can compromise or entirely eliminate an individual's ability to perceive visual images, including trauma to the eye, infection, degeneration, vascular irregularities, and inflammatory problems. The central portion of the retina is known as the macula, which is responsible for central vision, fine visualization and color differentiation. The function of the macula may be adversely affected by age related macular degeneration (wet or dry), diabetic macular edema, idiopathic choroidal neovascularization, high myopia macular degeneration, or advanced retinitis pigmentosa, among other pathologies.
Age related macular degeneration typically causes a loss of vision in the center of the visual field. Macular degeneration occurs in “wet” and “dry” forms. Taken together, these diseases affect approximately 1.75 million people in the U.S. alone. The prevalence of those blinded by AMD is expected to increase to over 2.95 million by 2020. (See e.g., Friedman, D S et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004; 122:564-72.) In the dry form, cellular debris (drusen) accumulates between the retina and the choroid, the blood supply of the outer retina, due to the inability of diseased RPE cells of phagocytosing photoreceptor (PR) shed outer disc segments. Resulting hardened lipids (lipofuscin) impede the reciprocal exchange of nutrients and waste products between the retina and choroid, and lead to PR death. In the more severe wet form, newly formed blood vessels from the choroid infiltrate the space behind the macula. The walls of these newly formed vessels are mechanically weak, and extremely susceptible to rupture. Hemorrhage usually results in loss of vision extremely quickly compared with dry AMD. In conjunction with the loss of functional cells in the eye, the newly formed blood vessels are fragile and often leak blood and interstitial fluid, which can further damage the macula.
While diseases that cause damage to specific cells or tissues are clear candidates for cellular therapy, there remains a need in the art for methods, substrates, and tools to improve the efficacy of cellular therapy.